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| PMID |
|
|
| TITLE |
|
| Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis. |
|
| ABSTRACT |
|
| OBJECTIVE |
NlmCategory: OBJECTIVE |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. |
| DESIGN |
NlmCategory: METHODS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. |
| SETTING |
NlmCategory: METHODS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. |
| SUBJECT(S) |
NlmCategory: METHODS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. |
| INTERVENTION(S) |
NlmCategory: METHODS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. |
| MAIN OUTCOME MEASURE(S) |
NlmCategory: METHODS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Allele frequency differences between cases and controls. |
| RESULT(S) |
NlmCategory: RESULTS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Allele frequency differences between cases and controls. Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study. |
| CONCLUSION(S) |
NlmCategory: CONCLUSIONS |
| To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Case-control study. Academic research. The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Allele frequency differences between cases and controls. Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study. Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases. |
| Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2013/10/16 |
| revised |
2014/04/10 |
| accepted |
2014/04/10 |
| entrez |
2014/05/07 06:00 |
| pubmed |
2014/05/07 06:00 |
| medline |
2014/09/30 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Painter JN |
|
Painter |
Jodie N |
JN |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: jodie.painter@qimrberghofer.edu.au. |
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Krause L |
|
Krause |
Lutz |
L |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Zhao ZZ |
|
Zhao |
Zhen Z |
ZZ |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Chapman B |
|
Chapman |
Brett |
B |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Zhang C |
|
Zhang |
Christine |
C |
|
Mater Medical Research Institute, Brisbane, Queensland, Australia. |
| Medland S |
|
Medland |
Sarah |
S |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Kennedy S |
|
Kennedy |
Stephen |
S |
|
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. |
| Treloar S |
|
Treloar |
Susan |
S |
|
Centre for Military and Veterans' Health, University of Queensland, Mayne Medical School, Queensland, Australia. |
| Zondervan K |
|
Zondervan |
Krina |
K |
|
Genetic and Genomic Epidemiology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 102 |
| ISSUE: 2 |
| TITLE: Fertility and sterility |
| ISOABBREVIATION: Fertil Steril |
| YEAR: 2014 |
| MONTH: Aug |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1556-5653 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Fertil Steril |
| COUNTRY: United States |
| ISSNLINKING: 0015-0282 |
| NLMUNIQUEID: 0372772 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 085235 |
Wellcome Trust |
United Kingdom |
| R01HD50537 |
NICHD NIH HHS |
United States |
| 084766 |
Wellcome Trust |
United Kingdom |
| R01 HD050537 |
NICHD NIH HHS |
United States |
| WT084766/Z/08/Z |
Wellcome Trust |
United Kingdom |
| WT085235/Z/08/Z |
Wellcome Trust |
United Kingdom |
| MR/K011480/1 |
Medical Research Council |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| CYP2C19 |
| Endometriosis |
| association |
| pooled sequencing |
| rs12248560 |
| rs4244285 |
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Aryl Hydrocarbon Hydroxylases |
genetics |
| Case-Control Studies |
genetics |
| Cytochrome P-450 CYP2C19 |
genetics |
| Endometriosis |
genetics |
| Exons |
genetics |
| Female |
genetics |
| Gene Frequency |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Heredity |
genetics |
| Humans |
genetics |
| Linkage Disequilibrium |
genetics |
| Pedigree |
genetics |
| Phenotype |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Promoter Regions, Genetic |
genetics |
| RNA Splice Sites |
genetics |
| Risk Factors |
genetics |
| Sequence Analysis, DNA |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
RNA Splice Sites |
| EC 1.14.14.1 |
Aryl Hydrocarbon Hydroxylases |
| EC 1.14.14.1 |
CYP2C19 protein, human |
| EC 1.14.14.1 |
Cytochrome P-450 CYP2C19 |
|
| OTHER ID's |
|
|
|
